Search Results (176)

Background/Objectives: Predicting comprehensive patient characteristics is essential for optimal individualized rehabilitation plans for acute stroke patients. However, current models primarily predict single outcomes. This study aimed to assess the applicability of latent class analysis (LCA) in rehabilitation practice by identifying comprehensive characteristics and associated predictors in acute stroke patients. Methods: We conducted a retrospective observational study using the Japan Association of Rehabilitation Database, including 10,270 stroke patients admitted to 37 acute-care hospitals between January 2005 and March 2016. Patients were classified using LCA based on outcomes at discharge, including Functional Independence Measure (FIM), National Institutes of Health Stroke Scale (NIHSS) subscales for upper-extremity function, length of hospitalization, and discharge destination. Predictor variables at admission included age, FIM scores, NIHSS subscales for upper-extremity function, stroke type, and daily rehabilitation volume. Results: 6881 patients were classified into nine distinct classes (class size: 4–29%). Class 1, representing the mildest cases, was noted for independent ambulation and good upper limb function. Class 2 comprised those with the most severe clinical outcome. Other classes exhibited a gradient of severity, commonly encountered in clinical practice. For instance, Class 7 included right-sided paralysis with preserved motor activities of daily living (ADLs) and modified dependence in cognitive functions, such as communication. All predictors at admission were significantly associated with class membership at discharge (p < 0.001). Conclusions: LCA effectively identified unique clinical subgroups among acute stroke patients and demonstrated that key admission variables could predict class membership. This approach offers a promising insight into targeted, personalized rehabilitation practice for acute stroke patients. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive disease that degeneratively damages both upper and lower motor neurons, eventually resulting in muscular paralysis and death. Although ALS is broad in scope and commonly thought of as a motor neuron disease, more active research sheds light on the that role skeletal muscle plays in the development and progression of the disease. Muscle tissue in ALS patients and in animal models demonstrates severe regenerative deficits, including impaired myogenesis and impaired myoblast fusion. In ALS, muscle stem cells, known as satellite cells, show poor performance in activation, proliferation, and differentiation and thus contribute to ALS muscle wasting. Moreover, the pathological tissue environment that inhibits myoblast fusion is made up of proinflammatory cytokines, oxidative stress, and a lack of trophic signals from the neuromuscular junction, which greatly disrupts homeostatic regulation. It is likely that skeletal muscle is instead a dynamic player, fueling neuromuscular degeneration as opposed to a passive responder to denervation. One must appreciate the cellular and molecular changes that complicate muscle regeneration in ALS for effective treatment to be developed, permitting simultaneous interventions with both muscle and neurons. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood–brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition. Full article

Background/Objectives: Myelomeningocele (MMC) is the most severe form of spina bifida, often accompanied by impaired motor function due to paralysis of the lower limbs, as well as neurogenic bladder (NB). These factors may contribute to nutritional disorders and cardiovascular diseases (CVDs) in the future. High-sensitivity CRP (hsCRP) is a positive marker of unstable atherosclerotic plaques and is commonly used in the diagnosis of CVDs. Adiponectin has an opposite, anti-inflammatory function. The aim of this study was to assess the risk of CVDs in a group of children with NB and a control group, based on serum levels of adiponectin, hsCRP, and lipid profiles. Methods: A prospective clinical estimation based on 87 children (67 NB, 20 control group) was conducted. Data collected from medical histories included the following: sex, age, anthropometric parameters (height, weight, BMI), level of spinal lesion, and activity according to Hoffer’s scale. Lipid profile values (cholesterol, HDL, LDL, triglycerides) were assessed using standard blood sample tests. hsCRP and adiponectin were measured using an ELISA kit. Results: A comparison of adiponectin and hsCRP levels revealed statistically significant differences between the NB group and the control. Additionally, significant correlations were identified between BMI and the biomarkers: hsCRP was positively associated with BMI, whereas adiponectin exhibited a negative association. The highest concentrations of hsCRP were detected in MMC patients with a Th lesion level and in non-walker patients. Conclusions: Elevated hsCRP may reflect increased cardiovascular risk in children with NB. While adiponectin levels were also altered, their association with cardiovascular risk appears more complex and may involve additional metabolic mechanisms. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventually death. The pathogenesis of ALS is influenced by genetic factors, environmental factors, and age-related dysfunctions. These factors, taken together, are responsible for sporadic cases of ALS, which account for approximately 85–90% of ALS cases, while familial ALS accounts for the remaining 10–15% of cases, usually with dominant traits. Despite advances in understanding and studying the disease, the cause of the onset of ALS remains unknown. Emerging evidence suggests that non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in the pathogenesis of the disease. An abnormal expression of these molecules is implicated in various ALS-related processes, including motor neuron survival, protein aggregation, and inflammation. Here, we describe the dysregulation of non-coding RNAs in the pathogenic mechanism of ALS, highlighting the potential roles of miRNAs, lncRNAs, and circRNAs as biomarkers or therapeutic targets to examine the progression of the disease. Full article

Spondylodiscitis is a devastating invasive infection that can lead to debilitating pain, motor weakness, or paralysis, even with appropriate medical and surgical treatment. Over the past two decades, there has been a worldwide increase in the incidence of spondylodiscitis, which can be attributed to a higher prevalence of various risk factors including intravenous drug use, hemodialysis, and spinal surgeries. The lumbar spine is the most likely region to be affected, with Staphylococcus aureus being the predominant pathogen. Management of spondylodiscitis requires a multi-disciplinary approach, with close coordination between the spinal surgeon and the infectious diseases specialist. Clinicians should become familiar with the epidemiology and presentation of patients with suspected spondylodiscitis because timely diagnosis and treatment may lead to improved outcomes. This unique review incorporates the perspectives from infectious disease and spine surgery specialists. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a rare, incurable, and fatal neurodegenerative disease that affects the muscles and results in paralysis. The onset and development of ALS involve complex interactions among metabolic signaling, genetic pathways, and external factors (epigenetics). New biomarkers and alternative therapeutic targets have been suggested; nonetheless, the results have been unsatisfactory. Mutations in SOD1, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43) have been identified in sporadic amyotrophic lateral sclerosis and approximately 12–20% of familial amyotrophic lateral sclerosis (fALS). Aim: This review analyzes dysregulated microRNA signaling pathways and their interactions with metabolic pathways in the context of ALS progression. Significance: Despite this, biomarkers remain unreliable, and the current medications prolong life without providing a cure. Some proposed approaches to control ALS progression include balancing autophagy and apoptosis, eliminating aggregated proteins, addressing mitochondrial dysfunction, and reducing inflammation. There is a need for studies on new biomarkers, medications, and therapeutic targets. In this context, deregulated circulating microRNAs are attracting attention for new studies on ALS at various phases of the disease. Despite the extensive literature on microRNAs as potential biomarkers for ALS, the proposition for translational clinical use remains limited. Studies have indicated a significant downregulation or upregulation of microRNAs in the motor neurons of ALS patients compared with those with other neurodegenerative disorders and healthy controls. The microRNA biogenesis highlights the importance of this study. MicroRNAs regulate protein synthesis (translation); all human cells express many microRNAs. The complementary structures of microRNA sequences and their mRNA targets allow them to significantly alter cellular and physiological processes. Studies have examined these microRNAs as potential biomarkers for several physiological states and diseases. Comments: The success of these studies may lead to simple, low-cost, and efficient solutions for controlling the progression of ALS and other degenerative diseases. As a result, it is challenging to identify a specific biomarker with total reliability, as a specific microRNA that is increased in one disease phase can decrease in another. These points require careful consideration. They exhibit several complexities and varied interactions, focusing on mRNA targets. The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Conclusions: The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis, and respiratory failure. This comprehensive review synthesizes the current knowledge on ALS pathophysiology, clinical heterogeneity, diagnostic frameworks, and evolving therapeutic strategies. Mechanistically, ALS arises from complex interactions between genetic mutations (e.g., in C9orf72, SOD1, TARDBP (TDP-43), and FUS) and dysregulated cellular pathways, including impaired RNA metabolism, protein misfolding, nucleocytoplasmic transport defects, and prion-like propagation of toxic aggregates. Phenotypic heterogeneity, manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates the rigorous application of the revised El Escorial criteria and emerging biomarkers such as neurofilament light chain. Clinically, ALS intersects with frontotemporal dementia (FTD) in up to 50% of the cases, driven by shared TDP-43 pathology and C9orf72 hexanucleotide expansions. Epidemiological studies have revealed a lifetime risk of 1:350, with male predominance (1.5:1) and peak onset between 50 and 70 years. Disease progression varies widely, with a median survival of 2–4 years post-diagnosis, underscoring the urgency for early intervention. Approved therapies, including riluzole (glutamate modulation), edaravone (antioxidant), and tofersen (antisense oligonucleotide), offer modest survival benefits, while dextromethorphan/quinidine alleviates the pseudobulbar affect. Non-pharmacological treatment advances, such as non-invasive ventilation (NIV), prolong survival by 13 months and improve quality of life, particularly in bulb-involved patients. Multidisciplinary care—integrating physical therapy, respiratory support, nutritional management, and cognitive assessments—is critical to addressing motor and non-motor symptoms (e.g., dysphagia, spasticity, sleep disturbances). Emerging therapies show promise in preclinical models. However, challenges persist in translating genetic insights into universally effective treatments. Ethical considerations, including euthanasia and end-of-life decision-making, further highlight the need for patient-centered communication and palliative strategies. Full article

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons in the brain and spinal cord, leading to muscle weakness, atrophy, and paralysis. Treatment focuses on symptom management, using medication, physiotherapy, and nutritional support. In this context, endoscopic gastrostomy (PEG) can provide adequate feeding, hopefully improving nutrition and preventing complications. Methods: We studied ALS patients undergoing PEG over three months post-procedure, using anthropometry ((BMI)—body mass index; (MUAC)—mid-upper arm circumference; (TSF)—tricipital skinfold; (MAMC)—mid-arm muscle circumference) and laboratory data (Albumin; Transferrin; total cholesterol and hemoglobin), evaluating survival, complications, and nutritional/clinical status. Statistical analysis included Kaplan–Meier survival estimation and Cox regression to assess nutritional markers associated with survival. Results: 150 ALS patients underwent gastrostomy, mostly older adults (mean age: 66.1 years; median: 67). Mean survival was 527 [95% CI: 432–622] days, median 318 [95% CI: 236–400]. ALS bulbar subtype, MUAC and MAMC positively impacted PEG-feeding survival time (p < 0.05, Wald test). During the first three months of PEG feeding, each unit increase (cm) in MUAC and MAMC lowered death risk by 10% and 11%, respectively, highlighting the importance of nutrition care for survival. The bulbar subtype showed higher PEG feeding survival, with a 55.3% lower death hazard than the spinal subtype. There were no major PEG complications. Conclusions: ALS patients present a high risk of malnutrition. Patients that improved MAMC and MUAC in the first three PEG-fed months presented longer survival. Early PEG nutrition, even when some oral feeding is still possible, may reinforce the preventative role of enteral feeding in maintaining nutrition and potentially improving survival. Full article

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. Although significant progress has been made in understanding ALS, its molecular mechanisms remain complex and multifactorial. This review explores the potential convergent mechanisms underlying ALS pathogenesis, focusing on the roles of key proteins including NEK1, C21ORF2, cyclin F, VCP, and TDP-43. Recent studies suggest that mutations in C21ORF2 lead to the stabilization of NEK1, while cyclin F mutations activate VCP, resulting in TDP-43 aggregation. TDP-43 aggregation, a hallmark of ALS, impairs RNA processing and protein transport, both of which are essential for neuronal function. Furthermore, TDP-43 has emerged as a key player in DNA damage repair, translocating to DNA damage sites and recruiting repair proteins. Given that NEK1, VCP, and cyclin F are also involved in DNA repair, this review examines how these proteins may intersect to disrupt DNA damage repair mechanisms, contributing to ALS progression. Impaired DNA repair and protein homeostasis are suggested to be central downstream mechanisms in ALS pathogenesis. Ultimately, understanding the interplay between these pathways could offer novel insights into ALS and provide potential therapeutic targets. This review aims to highlight the emerging connections between protein aggregation, DNA damage repair, and cellular dysfunction in ALS, fostering a deeper understanding of its molecular basis and potential avenues for intervention. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Consequent to the loss of these cells, neuromuscular functions decline, causing progressive weakness, muscle wasting, and paralysis, leading to death in 2 to 5 years. More than 90% of ALS cases are sporadic, while the remaining 10% of cases are familial, due to mutations in 40 different genes. One of the most common genes to be mutated in ALS is TARDBP (transactive response DNA binding protein 43), which encodes TDP-43 (TAR DNA-binding protein 43). A mutation in exon 6 of TARDBP causes the aminoacidic substitution G376D in the C-terminal region of TDP-43, leading to its cytoplasmic mislocalization and aggregation. In fibroblasts derived from patients carrying this mutation, we found a strong increase in lysosome number, with overexpression and higher nuclear translocation of the transcription factor TFEB. In contrast, lysosomal functionality was deeply compromised. Interestingly, lysosomal activity was unaffected at an early stage of the disease, worsening in more advanced stages. Moreover, we observed the same pathological phenotype in iPSC (induced pluripotent stem cells)-derived patient motor neurons carrying the G376D mutation. Therefore, this mutation compromises the functionality of lysosomes, possibly contributing to neurodegeneration. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to escalating muscle weakness, atrophy, and eventually paralysis. While neurons are the most visibly affected, emerging data highlight microglia—the brain’s resident immune cells—as key contributors to disease onset and progression. Rather than existing in a simple beneficial or harmful duality, microglia can adopt multiple functional states shaped by internal and external factors, including those in ALS. Collectively, these disease-specific forms are called disease-associated microglia (DAM). Research using rodent models, patient-derived cells, and human postmortem tissue shows that microglia can transition into DAM phenotypes, driving inflammation and neuronal injury. However, these cells can also fulfill protective roles under certain conditions, revealing their adaptable nature. This review explores recent discoveries regarding the multifaceted behavior of microglia in ALS, highlights important findings that link these immune cells to motor neuron deterioration, and discusses emerging therapies—some already used in clinical trials—that aim to recalibrate microglial functions and potentially slow disease progression. Full article

Background/Objective: Evaluating the upper limb function of the paretic and non-paretic sides of patients post-stroke is important for predicting the efficient use of the upper limbs in activities of daily living. Although there are evaluation methods that can quantify bilateral upper limb function, they are insufficient for understanding the motor characteristics of individual patients. In this study, we aimed to quantitatively evaluate bilateral upper limb function from the performance time of the cylinder transfer task of The Southampton Hand Assessment Procedure and to estimate the use status of the paralyzed upper limb. Methods: This cross-sectional study included 88 participants with hemiparesis post-stroke. Performance time in the three phases of the cylinder transfer task and the total performance time of these phases were measured. Moreover, existing upper limb function assessments were made. Results: The total performance time of the paralyzed side showed a significant correlation with the existing upper limb function assessments. A regression model was calculated to estimate the score of the existing upper limb function assessment from the performance time of each phase. Conclusions: This new evaluation method is a useful tool for monitoring the recovery of motor paralysis in patients post-stroke. It is our hope that clinicians will use these objective performance data to provide more effective rehabilitation treatment for patients recovering from stroke. Full article

Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset and motor function achieved. Patients with SMA type 3 (juvenile, Kugelberg-Welander disease) initially have the ability to walk unaided, but experience a gradual decline in motor abilities over time. However, their lifespan is not affected by the presence of the disease. Leptin, a cytokine-like hormone secreted by adipocytes, has receptors widely distributed in musculoskeletal tissues. Several studies suggest that adiponectin deficiency contributes to the development of insulin resistance, with lower adiponectin levels closely associated with greater insulin resistance and hyperinsulinemia. However, the role of adiponectin in different types of sarcopenia and its connection to insulin sensitivity remains controversial. The purpose of this study was to measure leptin and adiponectin levels in patients with SMA type 3 and explore their association with markers of insulin sensitivity. Methods: This cross-sectional study included 23 adult patients with SMA type 3 (SMA group) and 18 community-based healthy volunteers (control group), conducted from July 2020 to September 2024. Anthropometric parameters, body composition, body fat percentage, surrogate markers of insulin sensitivity (Homeostasis model assessment of insulin resistance index—HOMA-IR and ISI Matsuda), and circulating levels of leptin and adiponectin were measured in all participants. Results: Insulin resistance was present in 91.3% of patients with SMA type 3, as determined by HOMA-IR and ISI Matsuda insulin sensitivity markers. In the control group, 64.7% had insulin resistance (IR) according to HOMA-IR, while 44.4% met the ISI Matsuda criterion for IR, showing a significant difference in peripheral insulin sensitivity between groups. A significant difference in serum adiponectin levels was observed between patients with SMA type 3 and the control group, whereas there was no significant difference in serum leptin concentrations. High adiponectin levels were observed in 50% of patients with SMA type 3. In the healthy control group, adiponectin levels positively correlated with ISI Matsuda and negatively correlated with HOMA-IR, confirming the insulin-sensitizing role of adiponectin. However, this correlation was not observed in patients with SMA type 3. Conclusions: Our results suggest that in this specific type of hereditary neuromuscular disease, the interplay between sarcopenia and insulin leads to adiponectin resistance, challenging the canonical narrative between insulin sensitivity and adiponectin, and indicating a need for further research. Full article

Background: Dysphonia, a common symptom after thyroid surgery, is most often caused by damage to the recurrent laryngeal nerve. Laryngeal electromyography (LEMG) is used as a qualitative diagnostic tool to distinguish neurological etiology from other causes of dysphonia. The purpose of this study is to establish the value of LEMG as a predictor factor in the recovery of unilateral recurrent paralysis post-thyroidectomy. Methods: This study included 11 patients with unilateral vocal fold palsy (UVFP) evidenced on the videostrobolaryngoscopy (VSL) after thyroidectomy. Electrical activity of thyroarytenoid (TA) muscles of the patients included in the study was recorded through LEMG and the prognosis of the lesions was classified as excellent, fair, or poor based on the presence of spontaneous activity and motor unit recruitment. Results: LEMG at the first clinic visit showed an excellent prognosis in three of the cases, a fair prognosis in three of the cases, and five of them indicated a poor prognosis. At 6 months after the first LEMG, patients with a poor prognosis were unchanged and showed no LEMG improvement. Those with an excellent prognosis showed an increased recruitment response, and LEMG was normal. In one patient with a fair prognosis and minimal spontaneous activity, LEMG recruitment decreased during reevaluation. The other two fair-prognosis patients had a normal LEMG. Conclusions: A correlation was found between LEMG findings and functional recovery of the vocal cords, demonstrating that the presence of spontaneous activity represents a negative prognostic factor. However, due to limited patient cohorts, the sensitivity of the LEMG as a prognostic tool in the functional recovery of the larynx is not yet established and requires further research. Full article